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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

IL-17 Induction by ArtinM is Due to Stimulation of IL-23 and IL-1 Release and/or Interaction with CD3 in CD4(+) T Cells

Texto completo
Autor(es):
da Silva, Thiago Aparecido [1] ; Mariano, Vania Sammartino [1] ; Sardinha-Silva, Aline [1] ; de Souza, Maria Aparecida [1] ; Patriarca Mineo, Tiago Wilson [2] ; Roque-Barreira, Maria Cristina [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, BR-14049 Ribeirao Preto, SP - Brazil
[2] Univ Fed Uberlandia, Inst Ciencias Biomed, Av Engenheiro Dinz 1178, CP 593, BR-38400 Uberlandia, MG - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: PLoS One; v. 11, n. 2 FEB 22 2016.
Citações Web of Science: 6
Resumo

ArtinM is a D-mannose-binding lectin extracted from the seeds of Artocarpus heterophyllus that interacts with TLR2 N-glycans and activates antigen-presenting cells (APCs), as manifested by IL-12 production. In vivo ArtinM administration induces Th1 immunity and confers protection against infection with several intracellular pathogens. In the murine model of Candida albicans infection, it was verified that, in addition to Th1, ArtinM induces Th17 immunity manifested by high IL-17 levels in the treated animals. Herein, we investigated the mechanisms accounting for the ArtinM-induced IL-17 production. We found that ArtinM stimulates the IL-17 production by spleen cells in BALB/c or C57BL/6 mice, a response that was significantly reduced in the absence of IL-23, MyD88, or IL-1R. Furthermore, we showed that ArtinM directly induced the IL-23 mRNA expression and the IL-1 production by macrophages. Consistently, in cell suspensions depleted of macrophages, the IL-17 production stimulated by ArtinM was reduced by 53% and the exogenous IL-23 acted synergistically with ArtinM in promoting IL-17 production by spleen cell suspensions. We verified that the absence of IL-23, IL-1R, or MyD88 inhibited, but did not block, the IL-17 production by ArtinM-stimulated spleen cells. Therefore, we investigated whether ArtinM exerts a direct effect on CD4(+) T cells in promoting IL-17 production. Indeed, spleen cell suspensions depleted of CD4(+) T cells responded to ArtinM with very low levels of IL-17 release. Likewise, isolated CD4(+) T cells under ArtinM stimulus augmented the expression of TGF-beta mRNA and released high levels of IL-17. Considering the observed synergism between IL-23 and ArtinM, we used cells from IL-23 KO mice to assess the direct effect of lectin on CD4(+) T cells. We verified that ArtinM increased the IL-17 production significantly, a response that was inhibited when the CD4(+) T cells were pre-incubated with anti-CD3 antibody. In conclusion, ArtinM stimulates the production of IL-17 by CD4(+) T cells in two major ways: (I) through the induction of IL-23 and IL-1 by APCs and (II) through the direct interaction with CD3 on the CD4(+) T cells. This study contributes to elucidation of mechanisms accounting for the property of ArtinM in inducing Th17 immunity and opens new perspectives in designing strategies for modulating immunity by using carbohydrate recognition agents. (AU)

Processo FAPESP: 13/04088-0 - Lectinas de patógenos
Beneficiário:Maria Cristina Roque Antunes Barreira
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 12/12950-0 - Estudo das vias de sinalização desencadeadas pela interação de proteínas de micronema de Toxoplasma gondii com glicanos dos receptores do tipo Toll 2 e 4
Beneficiário:Aline Sardinha da Silva
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 06/60642-2 - Efeitos biológicos e aplicações farmacêuticas de lectinas
Beneficiário:Maria Cristina Roque Antunes Barreira
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 10/51763-6 - Maria Aparecida de Souza | Univ. Federal de Uberlandia / UFU - Brasil
Beneficiário:Maria Cristina Roque Antunes Barreira
Linha de fomento: Auxílio à Pesquisa - Pesquisador Visitante - Brasil
Processo FAPESP: 12/09611-0 - Efeito da lectina ArtinM sobre as células T CD4+ e T CD8+ murinas
Beneficiário:Thiago Aparecido da Silva
Linha de fomento: Bolsas no Brasil - Doutorado